Trait Document

Noonan syndrome is a genetic condition with characteristic facial features and birth defects. It is caused by mutations in the genes PTPN11, SOS1, RAF1, KRAS, BRAF, and MAP2K1, each of which makes a protein involved in human development.

Characteristics of Noonan syndrome

Noonan syndrome is a genetic condition with characteristic facial features such as, low set ears, widely spaced eyes, bright blue or blue-green eyes, a low hairline at the back of the head, and multiple congenital anomalies such as, heart defects, undescended testicles in males, kidney abnormalities, and an unusually shaped chest. Individuals with Noonan syndrome often have short stature, a broad or webbed neck, low set nipples, and bleeding problems. Varying degrees of developmental delay and/or intellectual disability are also commonly seen in individuals with Noonan syndrome.

Diagnosis/Testing

Most individuals with Noonan syndrome have a change or mutation in one of six genes: PTPN11, SOS1, RAF1, KRAS, BRAF, and MAP2K1. These genes are involved in a complex signaling pathway called the “RAS-MAPK pathway” which is important for the proper formation of many different types of tissue during human development. A mutation in any one of these genes disrupts this signaling pathway.

Management/Surveillance

Management and surveillance of individuals with Noonan syndrome often includes regular physical exams, eye exams, hearing evaluations, kidney ultrasound, blood tests, and ultrasound of the heart. Educational services are also recommended for individuals with learning disabilities/intellectual disability. Some studies suggest that individuals with Noonan syndrome are at increased risk of developing certain cancers such as leukemia.

Mode of inheritance

Noonan syndrome is inherited in an autosomal dominant pattern. This means inheriting one mutation is enough for an individual to be affected and show signs of Noonan syndrome. The mutation can be inherited from an affected parent or it can occur brand new (de novo) in an affected child.

Risk to family members

The risk to family members depends on whether or not the individual with Noonan syndrome has a parent affected with Noonan syndrome. If a parent also has Noonan syndrome, the risk of having a child with Noonan syndrome is 50% with each pregnancy. If a parent does not have Noonan syndrome, the risk of future pregnancies being affected is very low.

Special considerations

The clinical features of Noonan syndrome overlap with other genetic conditions such as Cardiofaciocutaneous syndrome (see trait profile) and Costello syndrome (see trait profile). Additionally, mutations in other genes (i.e., SHOC2, NRAS, and CBL) have been found in some individuals with features similar to Noonan syndrome.